[Show abstract][Hide abstract] ABSTRACT: The 22q13.3 deletion syndrome (Online Mendelian Inheritance in Man No. 606232) is a neurodevelopmental disorder that includes hypotonia, severely impaired development of speech and language, autistic-like behavior, and minor dysmorphic features. Although the number of reported cases is increasing, the 22q13.3 deletion remains underdiagnosed because of failure in recognizing the clinical phenotype and detecting the 22qter deletion by routine chromosome analyses. Our goal is to contribute to the description of the neurobehavioral phenotype and brain abnormalities of this microdeletional syndrome.
We assessed neuromotor, sensory, language, communication, and social development and performed cerebral MRI and study of regional cerebral blood flow measured by positron emission tomography in 8 children carrying the 22q13.3 deletion.
Despite variability in expression and severity, the children shared a common developmental profile characterized by hypotonia, sleep disorders, and poor response to their environment in early infancy; expressive language deficit contrasting with emergence of social reciprocity from ages approximately 3 to 5 years; sensory processing dysfunction; and neuromotor disorders. Brain MRI findings were normal or showed a thin or morphologically atypical corpus callosum. Positron emission tomography study detected a localized dysfunction of the left temporal polar lobe and amygdala hypoperfusion.
The developmental course of the 22q13.3 deletion syndrome belongs to pervasive developmental disorders but is distinct from autism. An improved description of the natural history of this syndrome should help in recognizing this largely underdiagnosed condition.
[Show abstract][Hide abstract] ABSTRACT: We describe four unrelated children who were referred to two tertiary referral medical genetics units between 1991 and 2005 and who are affected with juvenile polyposis of infancy. We show that these children are heterozygous for a germline deletion encompassing two contiguous genes, PTEN and BMPR1A. We hypothesize that juvenile polyposis of infancy is caused by the deletion of these two genes and that the severity of the disease reflects cooperation between these two tumor-suppressor genes.
The American Journal of Human Genetics 07/2006; 78(6):1066-74. · 11.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Kabuki syndrome (KS) is a rare MCA/MR syndrome with an estimated frequency of 1/32 000 in Japan. This syndrome is characterized by postnatal growth retardation, distinctive facial features, dermatoglyphic anomalies, skeletal dysplasia, and mental retardation. The molecular basis of KS remains unknown. Recently, Milunsky and Huang reported on six unrelated patients with a clinical diagnosis of KS and an 8p22-8p23.1 duplication using comparative genomic hybridization and BAC-FISH studies. Also, they suggested that a paracentric inversion may contribute to the occurrence of KS. In the present study, 24 patients with a clinical diagnosis of KS based on Niikawa-Kuroki criteria have been collected. They were tested for the presence of an 8p duplication using the same clones as described by Milunsky and Huang. Our results do not confirm the previously described association between KS and an 8p22-8p23.1 duplication.
European Journal of HumanGenetics 06/2005; 13(5):690-3. · 4.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report on two patients, a boy and a girl, with an additional Xq28 chromosome segment translocated onto the long arm of an autosome. The karyotypes were 46,XY,der(10)t(X;10)(q28;qter) and 46,XX,der(4)t(X;4)(q28;q34), respectively. In both cases, the de novo cryptic unbalanced X-autosome translocation resulted in a Xq28 chromosome functional disomy. To our knowledge, at least 17 patients with a distal Xq chromosome functional disomy have been described in the literature. This is the third report of a girl with an unbalanced translocation yielding such a disomy. When the clinical features of both patients are compared to those observed in patients reported in the literature, a distinct phenotype emerges including severe mental retardation, facial dysmorphic features with a wide face, a small mouth and a thin pointed nose, major axial hypotonia, severe feeding problems and proneness to infections. A clinically oriented FISH study using subtelomeric probes is necessary to detect such a cryptic rearrangement.
European Journal of HumanGenetics 06/2005; 13(5):579-85. · 4.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mesomelic dysplasia type Werner is defined by absence of tibiae and preaxial polysyndactyly of hands and feet. Occasional findings are triphalangeal thumbs, absence of patella(e), and dislocated fibula(e). The molecular basis is unknown and autosomal dominant inheritance with variable expressivity is currently postulated. Hirschsprung disease was reported previously in one case. We report here on a new case of mesomelic dysplasia Werner type associated with Hirschsprung disease and bilateral cryptorchidism. We discuss the overlap with the triphalangeal thumb polysyndactyly syndrome located in chromosome 7q36.
American Journal of Medical Genetics Part A 01/2004; 123A(2):186-9. · 2.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Overgrowth is rarely associated with chromosomal imbalances. Here we report on four children from two unrelated families presenting with overgrowth and a terminal duplication of the long arm of chromosome 15 diagnosed using cytogenetic and FISH studies. In both cases, chromosome analysis of the parents showed a balanced translocation involving 15q26.1-qter. Molecular and cytogenetic studies showed three copies of the insulin-like growth factor 1 receptor (IGF1R) gene. This finding suggests that overgrowth observed in our patients might be causally related to a dosage effect of the IGF1R gene, in contrast to severe growth retardation observed in patients with terminal deletion of 15q. The present observation emphasises the importance of chromosome analysis in patients with overgrowth and mental retardation. Moreover, it further delineates a specific phenotype related to trisomy 15q26.1-qter with macrosomia at birth, overgrowth, macrocephaly and mild developmental delay being the major clinical features.
European Journal of HumanGenetics 12/2002; 10(11):699-706. · 4.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We report a male patient presenting with the association of absent lacrimal ducts, distichiasis, dysmorphic facial features and limb abnormalities. Extensive chromosomal studies showed normal chromosomes. We discuss differential diagnoses such as Setleis, Char and Lacrimo-Auriculo-Dento-Digital (LADD) syndromes. This may represent a novel entity for which parental consanguinity would support an autosomal recessive mode of inheritance.